A Pathophysiological Study of the Postprandial Human Liver (PLS) (PLS)

Fatty liver disease is a globally widespread disease. The identification of valid biomarkers and targets for potential treatments requires in-depth knowledge about the pathophysiology of the postprandial liver. The study will consist of seven work packages (WP) including blood tests and liver biopsies taken after fasting or ingestion of a standardized meal in: healthy controls (WP 1), patients with NAFLD (WP 2), and patients with cirrhosis (WP 3) ; before and after a standardised meal in healthy controls (WP 4), and before and after glucagon in healthy controls (WP5), patients with NAFLD (WP6), and patients with T2DM and NAFLD (WP7).

Study Overview

• Status: Completed
• Conditions: Fatty Liver; Cirrhosis
• Intervention / Treatment: Dietary supplement: Standardised meal; Drug: Glucagon bolus

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Capital Region Denmark
    • Hvidovre, Capital Region Denmark, Denmark, 2650
      • Gastrounit, Copenhagen University Hospital Hvidovre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Study Population

We will include partcipants with suspected NAFLD or cirrhosis based on clinical assessments referred for a liver biopsy and healthy controls.

Description

Healthy participants (WP1 , WP4 , WP5 ):

Inclusion criteria: Healthy adults, 20 - 40 years old, non-smoker, BMI 20-25 kg/m2 , no chro-nical illnesses, no medication. Exclusion criteria: Blood donation within the past 3 months, acute illness within 2 weeks.

NAFLD (WP2, WP6):

Inclusion criteria: Patients with clinical diagnosis of NAFL and indication for liver biopsy. Exclusion criteria: Malignant disease, acute illness within the past 2 weeks.

Cirrhosis (WP 3):

Inclusion criteria: Patients with clinical diagnosis of cirrhosis and indication for liver biopsy. Exclusion criteria:Malignant disease, acute illness within the past 2 weeks.

T2DM and NAFLD (WP7):

Inclusion criteria: Patients with clinical diagnosis of T2DM and NAFL and indication for liver biopsy. Exclusion criteria: Malignant disease, acute illness within the past 2 weeks and use of insulin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood tests and liver biopsies after fasting or ingestion of a standardized meal; Participants randomized to the meal group consume, over a period of five minutes, a standardized liquid meal (Nutridrink Standard, 200 mL, 300 kcal, Nutricia). Participants randomized to the fasting group remain fasted for one hour after arrival. A transjugular liver biopsy is then performed at minute 60. Blood samples are obtained throughout the study day.	Dietary supplement: Standardised meal; Standardised meal (Nutridrink, Nutricia, 300 kcal, 18.4 g carbohydrates, 5.8 g fat, 12 g protein).
Experimental: Blood tests and liver biopsies before and after a standardized meal; A transjugular liver biopsy is performed, followed by ingestion of a standardized liquid meal (Nutridrink Standard, 200 mL, 300 kcal, Nutricia; 16% protein, 49% carbohydrate, 35% fat). A second transjugular liver biopsy is then performed 30 minutes after meal ingestion. Blood samples are obtained throughout the study day.	Dietary supplement: Standardised meal; Standardised meal (Nutridrink, Nutricia, 300 kcal, 18.4 g carbohydrates, 5.8 g fat, 12 g protein).
Experimental: Blood tests and liver biopsies before and after a bolus of glucagon; A transjugular liver biopsy is performed, followed by an intravenous bolus of 0.2 mg glucagon. A second transjugular liver biopsy is then performed 30 minutes after meal ingestion. Blood samples are obtained throughout the study day.	Drug: Glucagon bolus; Intravenous bolus of 0.2 mg glucagon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial phosphoproteomic changes in liver tissue in healthy individuals	Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy individuals.	60 minutes after the meal administered at the study day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial phosphoproteomic changes in liver tissue between healthy participants and patients with cirrhosis or patients with NAFLD.	Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in patients with cirrhosis and in patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD.	60 minutes after the meal administered at the study day
Postprandial proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals and compared to patients with cirrhosis and patients with NAFLD	Proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy participants, patients with cirrhosis, and patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD.	60 minutes after the meal administered at the study day
Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with cirrhosis and patients with NAFLD	Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy individuals, patients with cirrhosis, and patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD.	120 minutes after the meal administered at the study day
Postprandial phosphoproteomics, proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals.	Phosphoproteomic, proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' (before) and 'postprandial' (after) samples in healthy participants (paired).	30 minutes after the meal administered at the study day
Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals.	Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' (before) and 'postprandial' (after) samples in in healthy participants (paired).	120 minutes after the meal administered at the study day
Effect of exogenous glucagon on changes in liver phosphoproteomics, proteomics, metabolomics, and transcriptomics in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD.	Phosphoproteomic, proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted'/baseline samples and samples obtained after glucagon injection (paired) in healthy individuals, in patients with NAFLD, and in patients with T2DM and NAFLD and between healthy participants and patients with NAFLD and patients with T2DM and NAFLD.	30 minutes after the glucagon administered at the study day
Effect of exogenous glucagon on changes in phosphoproteomics, proteomics, metabolomics and peptidomic in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD	Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted'/baseline samples and samples obtained after glucagon injection (paired) in healthy individuals, in patients with NAFLD, and in patients with T2DM and NAFLD and between healthy participants and patients with NAFLD and patients with T2DM and NAFLD.	120 minutes after the glucagon administered at the study day

Collaborators and Investigators

• Sponsor: Copenhagen University Hospital, Hvidovre
• Collaborators: University of Copenhagen
• Investigators: Principal Investigator: Nicolai Jacob Wewer Albrechtsen, MD, Assoc. Prof., NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Principal Investigator: Lise Lotte Gluud, MD, Prof, Gastrounit, Copenhagen University Hospital Hvidovre, Denmark

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2019
• Primary Completion (Actual): August 21, 2025
• Study Completion (Actual): September 1, 2025

Study Registration Dates

• First Submitted: February 20, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (Actual): February 21, 2019

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Liver Diseases; Pathological Conditions, Signs and Symptoms; Fibrosis; Fatty Liver; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucagon
• Other Study ID Numbers: H-18052725

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No